ALSFTD

ALSFTD refers to the overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), recognizing a spectrum of neurodegenerative disease in which motor neuron symptoms coexist with frontal lobe–related cognitive and behavioral changes. The term is used to describe individuals who show features of both conditions or who shift along the continuum over time. It is not a single uniform disease but a shared clinical and pathological spectrum with overlapping genetic factors.

Clinical features typically include a combination of motor signs such as progressive limb weakness, muscle atrophy, fasciculations, spasticity, and dysarthria, along with behavioral and cognitive symptoms like apathy, disinhibition, impaired executive function, language difficulties, and changes in personality. The presentation can be predominantly ALS with cognitive impairment or predominantly FTD with emerging motor signs.

Genetics and pathology: a major genetic contributor is the hexanucleotide repeat expansion in C9orf72, found in a substantial subset of ALS-FTD cases. Other ALS/FTD-related genes include those encoding TAR DNA-binding protein 43 (TDP-43) and, less commonly, others such as SOD1 or FUS in certain individuals. Neuropathology typically shows TDP-43 proteinopathy with characteristic subtypes that reflect patterns of neuronal inclusions.

Diagnosis involves clinical assessment, neuropsychological testing, and neuroimaging, often supported by genetic testing, especially when there is a family history or early onset. MRI may reveal frontal and temporal lobe atrophy; PET can show corresponding hypometabolism.

Management is multidisciplinary and supportive, as there is no cure. Treatments for motor symptoms, such as riluzole or edaravone for ALS aspects, may be used, alongside physical, occupational, and speech therapy, and management of behavioral symptoms. Prognosis is variable; overall survival from onset typically ranges from several years, with FTD features potentially influencing disease course and care needs.